REVIEW article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1642091
This article is part of the Research TopicTumor-Associated Macrophages and Tumor-Infiltrating Lymphocytes in the Tumor MicroenvironmentView all 7 articles
Tumor-Associated Macrophages in Colon Cancer Immunotherapy: Mechanisms, Natural Product Interventions, and Microenvironment Remodeling
Provisionally accepted
- 1Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
- 2Chengdu University of Traditional Chinese Medicine, Chengdu, China
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Colon cancer persists as a major global health burden due to therapy resistance and metastasis, with tumorassociated macrophages (TAMs) in the microenvironment driving progression through immune evasion and angiogenesis. This review highlights plant-derived therapeutics targeting TAMs to disrupt protumor signaling. Key phytochemicals (e.g., Curcumin, Cucurbitacin B, Astragaloside IV) suppress M2 polarization via NF-κB/STAT3 inhibition, block VEGF/HIF-1α-mediated angiogenesis, and enhance antitumor immunity by downregulating PD-L1. Cannabidiol, Hydroxygenkwanin regulate TAM metabolism. Dietary agents like sulforaphane and β-glucans modulate TAM-gut microbiome crosstalk. Nanoparticle-encapsulated phytochemicals enhance TAM-targeted delivery, while clinical translation requires standardized phytopreparations and biomarker-guided trials. We propose integrating validated botanical adjuvants (e.g., Fucoidan for TLR4 inhibition, dihydroisotanshinone I for CCL2 suppression) with immunotherapies to remodel immunosuppressive niches. Phytotherapy offers a multifaceted strategy to overcome TAM-driven therapeutic barriers in colorectal cancer, emphasizing plant-based precision medicine to augment conventional treatments.
Keywords: Tumor-associated macrophages, Colon Cancer, phytochemicals, Immune checkpoint, Nanoparticle delivery
Received: 06 Jun 2025; Accepted: 23 Jul 2025.
Copyright: © 2025 He, Xiang, Luo, Wang, Zheng, Gao and Yao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Huan Yao, Chengdu University of Traditional Chinese Medicine, Chengdu, China
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